tbuckley/cabot-search huggingface dataset:
Systematic review and meta-analysis comparing educational and reminder digital interventions for promoting HPV vaccination uptake
Authors: Nutthaporn Chandeying, Therdpong Thongseiratch
Journal: npj Digital Medicine (2023)

Abstract Global Human papillomavirus (HPV) vaccination rates remain low despite available WHO-approved vaccines. Digital interventions for promoting vaccination uptake offer a scalable and accessible solution to this issue. Here we report a systematic review and meta-analysis examining the efficacy of digital interventions, comparing educational and reminder approaches, for promoting HPV vaccination uptake (HVU). This study also identifies factors influencing the effectiveness of these interventions. We searched PubMed, PsycInfo, Web of Science, and the Cochrane Library from each database’s inception to January 2023. Three raters independently evaluate the studies using a systematic and blinded method for resolving disagreements. From 1929 references, 34 unique studies (281,280 unique participants) have sufficient data. Client reminder (OR, 1.41; 95% CI, 1.23–1.63; P &lt; 0.001), provider reminder (OR, 1.39; 95% CI, 1.11–1.75; P = 0.005), provider education (OR, 1.18; 95% CI, 1.05–1.34; P = 0.007), and client education plus reminder interventions (OR, 1.29; 95% CI, 1.04–1.59; P = 0.007) increase HVU, whereas client education interventions do not (OR, 1.08; 95% CI, 0.92–1.28; P = 0.35). Digital intervention effectiveness varies based on participants’ gender and the digital platform used. Interventions targeting male or mixed-gender participants demonstrate greater benefit, and reminder platforms (SMS, preference reminders, or electronic health record alerts) are more effective in increasing HVU. Digital interventions, particularly client and provider reminders, along with provider education, prove significantly more effective than client education alone. Incorporating digital interventions into healthcare systems can effectively promote HPV vaccination uptake. Reminder interventions should be prioritized for promoting HVU.
Endoscopy E-Videos – recently published
Journal: Endoscopy (2023)

Comment on: Peroral submucosal endoscopic stricturotomy – a novel third-space approach for a complex anastomotic strictureEndoscopy 2023; 55(S 01): E656-E656DOI: 10.1055/a-2063-3465 Comment on: When obesity treatment goes too far: nutritional and endoscopic management of bariatric surgery complicationsEndoscopy 2023; 55(S 01): E647-E648DOI: 10.1055/a-2061-7173 Comment on: Tips and tricks for endoscopic ultrasound-guided hepaticogastrostomyEndoscopy 2023; 55(S 01): E643-E644DOI: 10.1055/a-2057-0460 Comment on: Cold snaring for gastric sampling and for colonic adenoma resection: an ecological tip to use a single device for the whole endoscopy procedureEndoscopy 2023; 55(S 01): E680-E681DOI: 10.1055/a-2067-4538
Incidence of Neonatal Hypothermia in the Newborn Nursery and Associated Factors
Authors: Rebecca Dang, Anisha I. Patel, Yingjie Weng, Alan R. Schroeder, Henry C. Lee, Janelle Aby, Adam Frymoyer
Journal: JAMA Network Open (2023)

Importance Thermoregulation is a key component of well-newborn care. There is limited epidemiologic data on hypothermia in late preterm and term infants admitted to the nursery. Expanding on these data is essential for advancing evidence-based care in a population that represents more than 3.5 million births per year in the US. Objective To examine the incidence and factors associated with hypothermia in otherwise healthy infants admitted to the newborn nursery following delivery. Design, Setting, and Participants A retrospective cohort study using electronic health record data from May 1, 2015, to August 31, 2021, was conducted at a newborn nursery at a university-affiliated children’s hospital. Participants included 23 549 infants admitted to the newborn nursery, from which 321 060 axillary and rectal temperature values were analyzed. Exposures Infant and maternal clinical and demographic factors. Main Outcomes and Measures Neonatal hypothermia was defined according to the World Health Organization threshold of temperature less than 36.5 °C. Hypothermia was further classified by severity (mild: single episode, temperature 36.0-36.4 °C; moderate/severe: persistent or recurrent hypothermia and/or temperature &amp;amp;lt;36.0 °C) and timing (early: all hypothermic episodes occurred within the first 24 hours after birth; late: any episode extended beyond the first 24 hours). Results Of 23 549 included infants (male, 12 220 [51.9%]), 5.6% were late preterm (35-36 weeks’ gestation) and 4.3% were low birth weight (≤2500 g). The incidence of mild hypothermia was 17.1% and the incidence of moderate/severe hypothermia was 4.6%. Late hypothermia occurred in 1.8% of infants. Lower birth weight and gestational age and Black and Asian maternal race and ethnicity had the highest adjusted odds across all classifications of hypothermia. The adjusted odds ratios of moderate/severe hypothermia were 5.97 (95% CI 4.45-8.00) in infants with a birth weight less than or equal to 2500 vs 3001 to 3500 g, 3.17 (95% CI 2.24-4.49) in 35 week’ vs 39 weeks’ gestation, and 2.65 (95% CI 1.78-3.96) in infants born to Black mothers and 1.94 (95% CI 1.61-2.34) in infants born to Asian mothers vs non-Hispanic White mothers. Conclusions and Relevance In this cohort study of infants in the inpatient nursery, hypothermia was common, and the incidence varied by hypothermia definition applied. Infants of lower gestational age and birth weight and those born to Black and Asian mothers carried the highest odds of hypothermia. These findings suggest that identifying biological, structural, and social determinants of hypothermia is essential for advancing evidence-based equitable thermoregulatory care.
Triage Procedures for Critical Care Resource Allocation During Scarcity
Authors: Jackson S. Ennis, Kirsten A. Riggan, Nicholas V. Nguyen, Daniel B. Kramer, Alexander K. Smith, Daniel P. Sulmasy, Jon C. Tilburt, Susan M. Wolf, Erin S. DeMartino
Journal: JAMA Network Open (2023)

During the COVID-19 pandemic, many US states issued or revised pandemic preparedness plans guiding allocation of critical care resources during crises. State plans vary in the factors used to triage patients and have faced criticism from advocacy groups due to the potential for discrimination.To analyze the role of comorbidities and long-term prognosis in state triage procedures.This cross-sectional study used data gathered from parallel internet searches for state-endorsed pandemic preparedness plans for the 50 US states, District of Columbia, and Puerto Rico (hereafter referred to as states), which were conducted between November 25, 2021, and June 16, 2023. Plans available on June 16, 2023, that provided step-by-step instructions for triaging critically ill patients were categorized for use of comorbidities and prognostication.Prevalence and contents of lists of comorbidities and their stated function in triage and instructions to predict duration of postdischarge survival.Overall, 32 state-promulgated pandemic preparedness plans included triage procedures specific enough to guide triage in clinical practice. Twenty of these (63%) included lists of comorbidities that excluded (11 of 20 [55%]) or deprioritized (8 of 20 [40%]) patients during triage; one state's list was formulated to resolve ties between patients with equal triage scores. Most states with triage procedures (21 of 32 [66%]) considered predicted survival beyond hospital discharge. These states proposed different prognostic time horizons; 15 of 21 (71%) were numeric (ranging from 6 months to 5 years after hospital discharge), with the remaining 6 (29%) using descriptive terms, such as long-term.In this cross-sectional study of state-promulgated critical care triage policies, most plans restricted access to scarce critical care resources for patients with listed comorbidities and/or for patients with less-than-average expected postdischarge survival. This analysis raises concerns about access to care during a public health crisis for populations with high burdens of chronic illness, such as individuals with disabilities and minoritized racial and ethnic groups.
MYC is a clinically significant driver of mTOR inhibitor resistance in breast cancer
Authors: Jinhyuk Bhin, Julia Yemelyanenko, Xue Chao, Sjoerd Klarenbeek, Mark Opdam, Yuval Malka, Liesbeth Hoekman, Dinja Kruger, Onno Bleijerveld, Chiara S. Brambillasca, Justin Sprengers, Bjørn Siteur, Stefano Annunziato, Matthijs J. van Haren, Nathaniel I. Martin, Marieke van de Ven, Dennis Peters, Reuven Agami, Sabine C. Linn, Epie Boven, Maarten Altelaar, Jos Jonkers, Daniel Zingg, Lodewyk F.A. Wessels
Journal: The Journal of Experimental Medicine (2023)

Targeting the PI3K-AKT-mTOR pathway is a promising therapeutic strategy for breast cancer treatment. However, low response rates and development of resistance to PI3K-AKT-mTOR inhibitors remain major clinical challenges. Here, we show that MYC activation drives resistance to mTOR inhibitors (mTORi) in breast cancer. Multiomic profiling of mouse invasive lobular carcinoma (ILC) tumors revealed recurrent Myc amplifications in tumors that acquired resistance to the mTORi AZD8055. MYC activation was associated with biological processes linked to mTORi response and counteracted mTORi-induced translation inhibition by promoting translation of ribosomal proteins. In vitro and in vivo induction of MYC conferred mTORi resistance in mouse and human breast cancer models. Conversely, AZD8055-resistant ILC cells depended on MYC, as demonstrated by the synergistic effects of mTORi and MYCi combination treatment. Notably, MYC status was significantly associated with poor response to everolimus therapy in metastatic breast cancer patients. Thus, MYC is a clinically relevant driver of mTORi resistance that may stratify breast cancer patients for mTOR-targeted therapies.
Estimating Sepsis Incidence Using Administrative Data and Clinical Medical Record Review
Authors: Lisa Mellhammar, Erik Wollter, Jacob Dahlberg, Benjamin Donovan, Carl-Johan Olséen, Per Ola Wiking, Norman Rose, Daniel Schwarzkopf, Marcus Friedrich, Carolin Fleischmann-Struzek, Konrad Reinhart, Adam Linder
Journal: JAMA Network Open (2023)

Despite the large health burden, reliable data on sepsis epidemiology are lacking; studies using International Statistical Classification of Diseases and Related Health Problems (ICD)-coded hospital discharge diagnosis for sepsis identification suffer from limited sensitivity. Also, ICD data do not allow investigation of underlying pathogens and antimicrobial resistance.To generate reliable epidemiological estimates by linking data from a population-based database to a reference standard of clinical medical record review.This was a retrospective, observational cohort study using a population-based administrative database including all acute care hospitals of the Scania region in Sweden in 2019 and 2020 to identify hospital-treated sepsis cases by ICD codes. From this database, clinical medical records were also selected for review within 6 strata defined by ICD discharge diagnosis (both with and without sepsis diagnosis). Data were analyzed from April to October 2022.Hospital and population incidences of sepsis, case fatality, antimicrobial resistance, and temporal dynamics due to COVID-19 were assessed, as well as validity of ICD-10 case identification methods compared with the reference standard of clinical medical record review.Out of 295 531 hospitalizations in 2019 in the Scania region of Sweden, 997 patient medical records were reviewed, among which 457 had sepsis according to clinical criteria. Of the patients with clinical sepsis, 232 (51%) were female, and 357 (78%) had at least 1 comorbidity. The median (IQR) age of the cohort was 76 (67-85) years. The incidence of sepsis in hospitalized patients according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria in 2019 was 4.1% (95% CI, 3.6-4.5) by medical record review. This corresponds to an annual incidence rate of 747 (95% CI, 663-832) patients with sepsis per 100 000 population. No significant increase in sepsis during the COVID-19 pandemic nor a decrease in sepsis incidence when excluding COVID-19 sepsis was observed. Few sepsis cases caused by pathogens with antimicrobial resistance were found. The validity of ICD-10-based case identification in administrative data was low.In this cohort study of sepsis epidemiology, sepsis was a considerable burden to public health in Sweden. Supplying administrative data with information from clinical medical records can help to generate reliable data on sepsis epidemiology.
Patient-derived enteroids provide a platform for the development of therapeutic approaches in microvillus inclusion disease
Authors: Meri Kalashyan, Krishnan Raghunathan, Haley Oller, Marie-Theres Bayer, Lissette Jimenez, Joseph T. Roland, Elena Kolobova, Susan J. Hagen, Jeffrey D. Goldsmith, Mitchell D. Shub, James R. Goldenring, Izumi Kaji, Jay R. Thiagarajah
Journal: Journal of Clinical Investigation (2023)

Microvillus inclusion disease (MVID), caused by loss-of-function mutations in the motor protein myosin Vb (MYO5B), is a severe infantile disease characterized by diarrhea, malabsorption, and acid/base instability, requiring intensive parenteral support for nutritional and fluid management. Human patient-derived enteroids represent a model for investigation of monogenic epithelial disorders but are a rare resource from MVID patients. We developed human enteroids with different loss-of function MYO5B variants and showed that they recapitulated the structural changes found in native MVID enterocytes. Multiplex immunofluorescence imaging of patient duodenal tissues revealed patient-specific changes in localization of brush border transporters. Functional analysis of electrolyte transport revealed profound loss of Na+/H+ exchange (NHE) activity in MVID patient enteroids with near-normal chloride secretion. The chloride channel-blocking antidiarrheal drug crofelemer dose-dependently inhibited agonist-mediated fluid secretion. MVID enteroids exhibited altered differentiation and maturation versus healthy enteroids. γ-Secretase inhibition with DAPT recovered apical brush border structure and functional Na+/H+ exchange activity in MVID enteroids. Transcriptomic analysis revealed potential pathways involved in the rescue of MVID cells including serum/glucocorticoid-regulated kinase 2 (SGK2) and NHE regulatory factor 3 (NHERF3). These results demonstrate the utility of patient-derived enteroids for developing therapeutic approaches to MVID.
Proof of Concept for Continuous On-Demand Phrenic Nerve Stimulation to Prevent Diaphragm Disuse during Mechanical Ventilation (STIMULUS): A Phase 1 Clinical Trial
Authors: Idunn S. Morris, Thiago Bassi, Catherine A. Bellissimo, Marc de Perrot, Laura Donahoe, Laurent Brochard, Nawzer Mehta, Viral Thakkar, Niall D. Ferguson, Ewan C. Goligher
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Proof of Concept for Continuous On-Demand Phrenic Nerve Stimulation to Prevent Diaphragm Disuse during Mechanical Ventilation (STIMULUS): A Phase 1 Clinical Trial." American Journal of Respiratory and Critical Care Medicine, 208(9), pp. 992–995
Patient‐level indirect treatment comparison of lanadelumab versus pdC1‐INH i.v. in hereditary angioedema patients: PATCH study
Authors: Markus Magerl, Guido Schiffhorst, Lena Fanter, Gerrit Müller, Christoph Hirche, Fabian Berkemeier, Emel Aygören
Journal: Allergy (2023)

Abstract Background Hereditary angioedema (HAE) is an autosomal dominant inherited disease in which patients suffer from local attacks primarily affecting skin and gastrointestinal tract, and sometimes even the upper respiratory tract leading to asphyxiation. Since head‐to‐head trials between authorized treatments are lacking, this study compares efficacy and safety of lanadelumab and intravenous plasma‐derived C1‐esterase inhibitor (pdC1‐INH i.v.) in HAE patients on long‐term prophylaxis by means of an indirect treatment comparison. Methods Efficacy and safety of lanadelumab against pdC1‐INH i.v. were analyzed in a fully prespecified indirect comparison based on individual patient data ( n = 231) from the HELP and CHANGE clinical trials. Primary and secondary efficacy endpoints were compared using a generalized linear model for count data. Confounding variables were identified a priori via systematic literature research and validated by clinical experts. Adjustment of confounders was implemented using a conditional regression model. Results Lanadelumab showed a statistically significant improvement in reduction of HAE attack rates compared to pdC1‐INH i.v. across multiple endpoints: Monthly attack rate of patients treated with lanadelumab was less than half compared to pdC1‐INH i.v. (Rate ratio: 0.486; 95% CI: 0.253, 0.932). Monthly rate of laryngeal attacks was found to be five times lower for lanadelumab (Rate ratio: 0.2; 95% CI: 0.044, 0.915) and monthly rate of acute treated HAE attacks among lanadelumab patients was about one third of the attack rate of pdC1‐INH i.v. patients (Rate ratio: 0.366; 95% CI: 0.185, 0.727). Conclusion This study contributes to current knowledge in the treatment of HAE by indicating a statistically significant reduction of HAE attacks under lanadelumab compared to pdC1‐INH i.v.
A novel molecular class that recruits HDAC/MECP2 complexes to PU.1 motifs reduces neuroinflammation
Authors: William T. Ralvenius, Alison E. Mungenast, Hannah Woolf, Margaret M. Huston, Tyler Z. Gillingham, Stephen K. Godin, Jay Penney, Hugh P. Cam, Fan Gao, Celia G. Fernandez, Barbara Czako, Yaima Lightfoot, William J. Ray, Adrian Beckmann, Alison M. Goate, Edoardo Marcora, Carmen Romero-Molina, Pinar Ayata, Anne Schaefer, Elizabeta Gjoneska, Li-Huei Tsai
Journal: The Journal of Experimental Medicine (2023)

Pervasive neuroinflammation occurs in many neurodegenerative diseases, including Alzheimer's disease (AD). SPI1/PU.1 is a transcription factor located at a genome-wide significant AD-risk locus and its reduced expression is associated with delayed onset of AD. We analyzed single-cell transcriptomic datasets from microglia of human AD patients and found an enrichment of PU.1-binding motifs in the differentially expressed genes. In hippocampal tissues from transgenic mice with neurodegeneration, we found vastly increased genomic PU.1 binding. We then screened for PU.1 inhibitors using a PU.1 reporter cell line and discovered A11, a molecule with anti-inflammatory efficacy and nanomolar potency. A11 regulated genes putatively by recruiting a repressive complex containing MECP2, HDAC1, SIN3A, and DNMT3A to PU.1 motifs, thus representing a novel mechanism and class of molecules. In mouse models of AD, A11 ameliorated neuroinflammation, loss of neuronal integrity, AD pathology, and improved cognitive performance. This study uncovers a novel class of anti-inflammatory molecules with therapeutic potential for neurodegenerative disorders.
Utilization and Spending With Preventive Drug Lists for Asthma Medications in High-Deductible Health Plans
Authors: Anna D. Sinaiko, Dennis Ross-Degnan, J. Frank Wharam, Robert F. LeCates, Ann Chen Wu, Fang Zhang, Alison A. Galbraith
Journal: JAMA Network Open (2023)

High-deductible health plans with health savings accounts (HDHP-HSAs) incentivize patients to use less health care, including necessary care. Preventive drug lists (PDLs) exempt high-value medications from the deductible, reducing out-of-pocket cost sharing; the associations of PDLs with health outcomes among patients with asthma is unknown.To evaluate the associations of a PDL for asthma medications on utilization, adverse outcomes, and patient spending for HDHP-HSA enrollees with asthma.This case-control study used matched groups of patients with asthma before and after an insurance design change using a national commercial health insurance claims data set from 2004-2017. Participants included patients aged 4 to 64 years enrolled for 1 year in an HDHP-HSA without a PDL in which asthma medications were subject to the deductible who then transitioned to an HDHP-HSA with a PDL that included asthma medications; these patients were compared with a matched weighted sample of patients with 2 years of continuous enrollment in an HDHP-HSA without a PDL. Models controlled for patient demographics and asthma severity and were stratified by neighborhood income. Analyses were conducted from October 2020 to June 2023.Employer-mandated addition of a PDL that included asthma medications to an existing HDHP-HSA.Outcomes of interest were utilization of asthma medications on the PDL (controllers and albuterol), asthma exacerbations (oral steroid bursts and asthma-related emergency department use), and out-of-pocket spending (all and asthma-specific).A total of 12 174 participants (mean [SD] age, 36.9 [16.9] years; 6848 [56.25%] female) were included in analyses. Compared with no PDL, PDLs were associated with increased rates of 30-day fills per enrollee for any controller medication (change, 0.10 [95% CI, 0.03 to 0.17] fills per enrollee; 12.9% increase) and for combination inhaled corticosteroid long-acting β2-agonist (ICS-LABA) medications (change, 0.06 [95% CI, 0.01 to 0.10] fills per enrollee; 25.4% increase), and increased proportion of days covered with ICS-LABA (6.0% [0.7% to 11.3%] of days; 15.6% increase). Gaining a PDL was associated with decreased out-of-pocket spending on asthma care (change, -$34 [95% CI, -$47 to -$21] per enrollee; 28.4% difference), but there was no significant change in asthma exacerbations and no difference in results by income.In this case-control study, reducing cost-sharing for asthma medications through a PDL was associated with increased adherence to controller medications, notably ICS-LABA medications used by patients with more severe asthma, but was not associated with improved clinical outcomes. These findings suggest that PDLs are a potential strategy to improve access and affordability of asthma care for patients in HDHP-HSAs.
ESGE news and upcoming events September 2023
Journal: Endoscopy (2023)

ESGE Research Grants support innovative, original research in gastroenterology. Potential contenders submit their research idea online. Our research committee reviews the applications and the top-rated proposals are selected. These applicants then take part in the ESGE Research Champions Den, at ESGE Days, where a jury of eminent researchers quiz the candidates, live. The best two or three are awarded research grants.